School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia.
Campbelltown Private Hospital, Campbelltown, NSW 2560, Australia.
Int J Mol Sci. 2020 Jun 25;21(12):4540. doi: 10.3390/ijms21124540.
Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such as chronic nausea and vomiting. As no cures are currently available, clinical care is limited to symptom management, while the underlying causes of impaired GI motility remain unaddressed. The efficient movement of contents through the GI tract is facilitated by peristalsis. These rhythmic slow waves of GI muscle contraction are mediated by several cell types, including smooth muscle cells, enteric neurons, telocytes, and specialised gut pacemaker cells called interstitial cells of Cajal (ICC). As ICC dysfunction or loss has been implicated in several GI motility disorders, ICC represent a potentially valuable therapeutic target. Due to their availability, murine ICC have been extensively studied at the molecular level using both normal and diseased GI tissue. In contrast, relatively little is known about the biology of human ICC or their involvement in GI disease pathogenesis. Here, we demonstrate human gastric tissue as a source of primary human cells with ICC phenotype. Further characterisation of these cells will provide new insights into human GI biology, with the potential for developing novel therapies to address the fundamental causes of GI dysmotility.
全世界数以百万计的患者患有胃肠道(GI)动力障碍,例如胃轻瘫。这些疾病通常包括使人衰弱的症状,如慢性恶心和呕吐。由于目前尚无治愈方法,临床护理仅限于症状管理,而未解决胃肠道动力受损的根本原因。通过蠕动促进胃肠道内容物的有效运动。这些胃肠道肌肉收缩的有节奏的缓慢波由几种细胞类型介导,包括平滑肌细胞、肠神经元、间质细胞(telocytes)和专门的肠道起搏细胞,称为 Cajal 间质细胞(ICC)。由于 ICC 功能障碍或缺失与几种胃肠道动力障碍有关,因此 ICC 代表了一个有潜在价值的治疗靶点。由于其可用性,使用正常和患病的胃肠道组织在分子水平上对鼠类 ICC 进行了广泛研究。相比之下,人们对人类 ICC 的生物学或它们在胃肠道疾病发病机制中的作用知之甚少。在这里,我们证明胃组织是具有 ICC 表型的原代人类细胞的来源。对这些细胞的进一步表征将为人类胃肠道生物学提供新的见解,并有可能开发新的疗法来解决胃肠道动力障碍的根本原因。